title: Elimination of endogenous toxin, creatinine from blood plasma depends on albumin conformation: site specific uremic toxicity & impaired drug binding.
abstract: Uremic syndrome results from malfunctioning of various organ systems due to the retention of uremic toxins which, under normal conditions, would be excreted into the urine and/or metabolized by the kidneys. The aim of this study was to elucidate the mechanisms underlying the renal elimination of uremic toxin creatinine that accumulate in chronic renal failure. Quantitative investigation of the plausible correlations was performed by spectroscopy, calorimetry, molecular docking and accessibility of surface area. Alkalinization of normal plasma from pH 7.0 to 9.0 modifies the distribution of toxin in the body and therefore may affect both the accumulation and the rate of toxin elimination. The ligand loading of HSA with uremic toxin predicts several key side chain interactions of site I that presumably have the potential to impact the specificity and impaired drug binding. These findings provide useful information for elucidating the complicated mechanism of toxin disposition in renal disease state.
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
authors.forename: Ankita
authors.initials: A
authors.lastname: Varshney
authors.forename: Mohd
authors.initials: M
authors.lastname: Rehan
authors.forename: Naidu
authors.initials: N
authors.lastname: Subbarao
authors.forename: Gulam
authors.initials: G
authors.lastname: Rabbani
authors.forename: Rizwan Hasan
authors.initials: RH
authors.lastname: Khan
mesh_terms: D000418:Albumins / Q000737:chemistry* / Q000378:metabolism*; D003404:Creatinine / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D004337:Drug Carriers / Q000378:metabolism; D004347:Drug Interactions / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D009928:Organ Specificity; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010949:Plasma / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D013696:Temperature; D013816:Thermodynamics; D014118:Toxins, Biological / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D014511:Uremia / Q000378:metabolism
chemical_list: D000418:Albumins; D004337:Drug Carriers; D004364:Pharmaceutical Preparations; D014118:Toxins, Biological; D003404:Creatinine